With the increasing use of transgenic and ES cell technology to produce models of human physiology and human diseases in mice, the ability to use sophisticated and technically demanding experimental methods to phenotype mouse models in vivo has become an increasingly important priority for investigators interested in diabetes. The demand for these services has increased dramatically at Washington University School of Medicine. In response to requests for help in characterizing mouse models of diabetes, the leadership of the DRTC decided to establish a new core laboratory devoted to this purpose. The Mouse Phenotyping Core will provide members of the DRTC with technical services designed to characterize the metabolic phenotypes of genetically engineered mice relevant to diabetes. Both type 1 and type 2 diabetes can alter the physiology of every mammalian tissue, but the pathogenesis of diabetes syndromes appears to be driven by dysfunction in several discrete organs: pancreatic islets, the liver, skeletal muscle, and adipose tissue. The genetic manipulation of mice is now routine, and many different groups have confirmed the suitability of reagents for directing gene expression in critical diabetes-related tissues. Members of the Washington University DRTC are actively generating transgenic mice using the RIP/rat insulin promoter (directing pancreatic beta cell expression), the albumin promoter (for liver expression), the myosin light chain 2 promoter (for skeletal muscle expression) and the aP2 promoter (for adipose expression). DRTC members recently reported transgenesis experiments addressing the role of the K(ATP) channels in insulin secretion (1), the insulin signaling molecule Aktl in beta cell growth (2), and provided proof of the concept that respiratory uncoupling in skeletal muscle could prevent obesity and diabetes (3). In addition to studies of tissues known to be central to pathogenesis of diabetes syndromes, members of the Washington University DRTC regularly inactivate genes in mice using homologous recombination techniques and uncover unexpected metabolic phenotypes. Several DRTC investigators are engineering mice to achieve tissue-specific gene inactivation using cre-loxP technology. By providing a common collection of services ideal for defining physiological mechanisms in mice, the Mouse Phenotyping Core will enhance the research productivity of DRTC investigators while decreasing the cost of diabetes research.